The objective of this research is the elucidation of the role of the protein and polypeptide hormones of the pituitary gland in the regulation of growth and function of normal and cancerous target cells. The emerging concept that certain protein hormones may stimulate cell proliferation through the mediation of cyclic GMP whereas other polypeptide hormones may inhibit replication and induce differentiation through the action of cyclic AMP, will be examined. The effects of highly purified and synthetic pituitary hormones on the growth and differentiation of fetal rat adrenal cortical cells, mouse tumor Leydig cells and rat mammary tumor cells maintained in tissue culture will be investigated in terms of various biochemical parameters, including polyamine and DNA synthesis, and cellular cyclic AMP and cyclic GMP concentrations. Binding of specifically tritiated ACTH to the adrenal cortical cell will be studied in order to understand the modulation of specific hormone receptors during ontogeny. BIBLIOGRAPHIC REFERENCES: Inhibition of replication of normal adrenocortical cells in culture by adrenocorticotropin. Ramachandran, J. and Suyama, A. T. Proc. Nat. Acad. Sci. 72, 113-117 (1975). The effects of interstitial cell-stimulating hormone. Its subunits and recombinants on isolated rat Leydig cells. Ramachandran, J. and Sairam, M.R. Arch. Biochem. Biophys. 167, 294-300 (1975).